A wide number of pathological conditions are characterized by oversecretion of gastric acid. Such conditions include, but are not limited to, Zollinger/Ellison syndrome (ZES), gastroesophageal reflux disease, peptic ulcer disease, duodenal ulcers, atrophic gastritis, esophagitis, and the like. Conditions such as ZES and peptic ulcers, in particular, can have serious complications and represent some of the most prevalent diseases in industrialized nations.
The treatment of such conditions often requires high and repeated doses of acid output (AO) inhibiting agents to effectively reduce intragastric acidity. Although histamine H2-antagonists have been used successfully to treat such conditions, the erratic and diminishing responses with these antagonists as well as the progressive occurrence of more sever side effects associated with the use of larger doses has led to the use of the more effective proton pump inhibitors (PPIs).
Proton pump inhibitors (PPI) are potent inhibitors of gastric acid secretion by inhibiting H+/K+-ATPase, the enzyme involved in the final step of hydrogen ion production in the parietal cells. Hence, PPI have been used in the treatment of gastric acid related diseases in humans. Despite their wide-spread use, means of increasing PPI efficacy, e.g. at a lower dose are desired.